Antibiotic therapy plays a vital role in modern medicine. The advent of antibiotic therapy in this century has, in part, been responsible for the increased life expectancy, as wel
Despite the availability of a variety of highly effective antibiotics, the search for improved agents is a continuing one for a variety of reasons. Many organisms become resistant to a particular antibiotic or class of antibiotics and thus new drug entities must be continually made available to treat infections involving strains of organisms which have become resistant to all other therapy. Apart from the problem of resistance, this powerful class of drugs has a number of undesirable side effects and thus the search continues for agents which are lower in toxicity than presently available antibiotics yet are effective antimicrobial agents.
Another problem with current antibiotic therapy is that there are certain organisms, such as the Proteus genus which are very difficult to eradicate. Thus researchers are constantly seeking new antibiotic entities which would be effective against various Proteus strains as well as strains of other pathogenic organisms.
Recently a new group of antibiotics has been identified and designated as the fortimicins.
Fortimicin A exhibits a wide range of in vitro activity against gram-positive and gram-negative bacteria and also exhibits excellent activity against strains of Staphylococcus aureus and Escherichia coli which are resistant to various known antibiotics such as kanamycin, gentamicin, tobramycin and the like, as well as exhibiting antibacterial activity against bacteria of the genus Proteus. In vivo tests indicate the ED.sub.50 of fortimicin A against Escherichia coli Juhl KY 4286 in mice to be 6 mg/kg (See U.S. Pat. No. 3,976,768).
Fortimicin B also exhibits in vitro antibacterial activity against various gram-positive and gram-negative antibiotics, but is considerably less active than fortimicin A. (See U.S. Pat. No. 3,931,400.) 4-N-Acyl and 4-N-alkyl derivatives of fortimicin B have also been developed.
Just as there has been a continuing need for new generations of aminoglycosides, penicillins, cephalosporins and other important antibiotics, there is a need for various fortimicin derivatives.
The present invention provides new derivatives of fortimicin A, fortimicin B, 4-N-acyl fortimicin B and 4-N-alkyl fortimicin B.